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Leukemia drug keeps working in continuous treatment schedule

Researchers have found a better way to give an important drug in the treatment of leukemia, PEGasparaginase. As a result, much fewer children with acute lymphoblastic leukemia (ALL) experience hypersensitivity to the drug, and it continues to work well more often. Onderzoeker Leiah Brigitha: ‘This new approach allows more children to complete the full course of PEGasparaginase, which contributes to a better chance of survival.’

Every year, 120 children in the Netherlands are diagnosed with ALL. PEGasparaginase is an important part of the treatment. But sometimes this medicine causes hypersensitivity in children with ALL. Sometimes the child gets a kind of allergic reaction. The drug may also stop working, with or without visible allergic symptoms in the child.

No break

Scientists in the Pieters group at the Princess Máxima Center studied whether a difference in treatment schedule could lower the risk of PEGasparaginase inactivation. They divided 312 children with ALL into two groups. All children first received initial treatment with PEGasparaginase. One group had a break before the follow-up treatment, while the other group immediately continued with the drug. The results of the study were recently published in the Journal of Clinical Oncology.

Finish the treatment

The researchers saw that four of the 155 children who received a continuous dose experienced hypersensitivity, compared to 17 of the 157 children who received a non-continuous dose. ‘The risk of PEGasparaginase inactivation was reduced by seven times,’ says Leiah Brigitha, who worked on the study as a PhD student in the Pieters group, and is now a postdoctoral scientist in the Huitema group. ‘And, importantly, the continuous treatment schedule was just as safe and effective as the previous method. This new approach ensures that children tolerate the drug better, which means more of them can complete the full course of PEGasparaginase. And that in turn contributes to a better chance of survival.’

Pediatric oncologist Dr. Inge van der Sluis, also involved in the research, adds: ‘Children for whom PEGasparaginase stops working need to switch to a comparable drug, erwinia asparaginase. This treatment has much more impact on families because it is given every other day. The continuous administration of PEGasparaginase thereby also indirectly improves children’s quality of life.’

Treatment protocol

Brigitha and Van der Sluis conducted the research within the ALL-11 treatment protocol, with which children were treated from 2012 to 2020. Brigitha: ‘We hope that the results of our research will in future lead to a change in the new treatment protocols, leading to a better outcome for children with ALL.’